The effect of water displacement on binding thermodynamics: Concanavalin A
The effect of water displacement on binding thermodynamics: Concanavalin A
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DOI：
10.1021/jp0477912
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发表时间：
2005-01-13
影响因子：
3.3
通讯作者：
Lazaridis, T
中科院分区：
文献类型：
--
作者：
Li, Z;Lazaridis, T
生物分子复合体结合界面上的相互作用通常是由有序水分子介导的。在这项工作中，我们考虑了两个刀豆蛋白A-碳水化合物复合体。在第一种情况下，水分子被埋在结合界面上。在第二种中，这种水分子被配体的修饰取代(Clarke，C.；Wood，R.J.；Gluska，J.；Cooper，A.；Nutley，M.A.；Boons，G.J.J.Am化学。SoC。2001年、第123、12238-12247)。我们利用能量和熵的统计力学公式和分子动力学模拟计算了这种水分子对热力学性质的贡献。还计算了对结合亲和力的其他贡献，包括去溶解、构象限制熵以及配体与蛋白质之间的相互作用。配位体修饰导致有序水分子置换的热力学结果与实验数据定性一致。水分子的自由能贡献(-17.2千卡/摩尔；-19.2焓和+2熵)与甘露糖苷2中附加的蛋白质-配体相互作用(-18.9千卡/摩尔)几乎相同。这两个结构离子与水的相互作用比与甘露糖苷2的羟基作用更强，从而有利于甘露糖苷1。与结合自由能差相比，解溶和构象熵的贡献要小得多，但却是显著的。出现的情况是，水置换的最终结果对结合部位的细节很敏感，不能用简单的经验规则来预测。
Interactions at the binding interface of biomolecular complexes are often mediated by ordered water molecules. In this work, we considered two concanavalin A-carbohydrate complexes. In the first, a water molecule is buried at the binding interface. In the second, this water molecule is displaced by a modification of the ligand (Clarke, C.; Woods, R. J.; Gluska, J.; Cooper, A.; Nutley, M. A.; Boons, G. J. J. Am. Chem. Soc. 2001, 123, 12238-12247). We computed the contribution of this water molecule to the thermodynamic properties using statistical mechanical formulas for the energy and entropy and molecular dynamics simulations. Other contributions to the binding affinity, including desolvation, entropy of conformational restriction, and interaction between the ligand and protein, were also computed. The thermodynamic consequences of displacement of the ordered water molecule by ligand modification were in qualitative agreement with experimental data. The free energy contribution of the water molecule (-17.2 kcal/mol; -19.2 enthalpic and +2 entropic) was nearly equivalent to the additional protein-ligand interactions in trimannoside 2 (-18.9 kcal/mol). The two structural ions interact more strongly with the water than with the hydroxyl of trimannoside 2, thus favoring trimannoside 1. The contributions from desolvation and conformational entropy are much smaller but significant, compared to the binding free energy difference. The picture that emerges is that the final outcome of water displacement is sensitive to the details of the binding site and cannot be predicted by simple empirical rules.